Skip to Main content Skip to Navigation
Journal articles

FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells

Abstract : Ubiquitination by serving as a major degradation signal of proteins, but also by controlling protein functioning and localization, plays critical roles in most key cellular processes. Here, we show that MITF, the master transcription factor in melanocytes, controls ubiquitination in melanoma cells. We identified FBXO32, a component of the SCF E3 ligase complex as a new MITF target gene. FBXO32 favors melanoma cell migration, proliferation, and tumor development in vivo. Transcriptomic analysis shows that FBXO32 knockdown induces a global change in melanoma gene expression profile. These include the inhibition of CDK6 in agreement with an inhibition of cell proliferation and invasion upon FBXO32 silencing. Furthermore, proteomic analysis identifies SMARC4, a component of the chromatin remodeling complexes BAF/PBAF, as a FBXO32 partner. FBXO32 and SMARCA4 co-localize at loci regulated by FBXO32, such as CDK6 suggesting that FBXO32 controls transcription through the regulation of chromatin remodeling complex activity. FBXO32 and SMARCA4 are the components of a molecular cascade, linking MITF to epigenetics, in melanoma cells.
Document type :
Journal articles
Complete list of metadatas

https://www.hal.inserm.fr/inserm-03138835
Contributor : Bertolotto-Ballotti Bertolotto-Ballotti <>
Submitted on : Thursday, February 11, 2021 - 2:36:50 PM
Last modification on : Thursday, February 25, 2021 - 10:11:22 AM

File

s41418-020-00710-x.pdf
Publication funded by an institution

Identifiers

Collections

Citation

Nadia Habel, Najla El-Hachem, Frédéric Soysouvanh, Hanene Hadhiri-Bzioueche, Serena Giuliano, et al.. FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells. Cell Death and Differentiation, Nature Publishing Group, 2020, Online ahead of print. ⟨10.1038/s41418-020-00710-x⟩. ⟨inserm-03138835⟩

Share

Metrics

Record views

49

Files downloads

21